196. Schizophrenia Patients Show Enhanced Responses to Loss Avoidance in Frontostriatal Circuits

摘要

>Background: In previous work (Gold et al., 2012), we found that, in the context of a reinforcement learning (RL) task, patients with schizophrenia (SZ) were more likely to subjectively value gains and instances of loss-avoidance similarly, although instances of loss-avoidance were objectively neutral. This finding was most true of avolitional SZ patients and was attributed to maladaptive representations of expected value (EV), in the presence of intact signaling of reward prediction errors (RPEs). In the current study, using fMRI, we investigated the neural basis of this phenomenon, hypothesizing that SZ patients would exhibit aberrant neural signals related to value-signaling in frontostriatal loops, rather than attenuated RPE signals. >Methods: We administered a variant of an RL paradigm (Pessiglione et al. 2006) to 27 chronic SZ patients and 27 controls. Participants learned three probabilistic discriminations (choice of the better stimulus led to better outcome 70% of the time, choice of the worse stimulus led to worse outcome 70% of the time). In a “Gain-Miss” pair, outcomes were either a gain of 25 cents neutral. In a “Loss-Avoid” pair, outcomes were either neutral or a loss of 25 cents. In a “Correct-Incorrect” pair, subjects received only “Correct” and “Incorrect” as pictorial feedback. We examined neural responses to outcomes in nodes of reward and salience networks identified a priori. We also examined contrasts in these areas between outcomes with the same RPE valence but different experienced values (GAIN – LOSS-AVOID, e.g.) and between outcomes with the same experienced value but different RPE valence (LOSS-AVOID – MISS, e.g.). >Results: We found that SZ patients showed ENHANCED [LOSS-AVOID – MISS] (RPE-valence) contrasts, relative to controls, in right ventral striatum [VS; t(52) = 2.005, P = .050]. We also observed that SZ patients showed REDUCED [GAIN – LOSS-AVOID] (outcome-valence) contrasts, relative to controls, in dorsal anterior cingulate cortex, dorsomedial prefrontal cortex, and bilateral anterior insula (all t’s > 2.5, all Ps < .02). The between-group differences in these contrasts were largely attributable to ENHANCED responses to loss-avoidance in SZ patients, rather than reduced responses to gains or misses. Finally, we observed significant correlations between neural signals evoked by loss-avoidance in right VS and both Avolition (r = .427) and Anhedonia/Asociality (r = .456) subscores from the SANS. >Conclusion: These results provide further evidence for intact RPE signaling in chronic, medicated SZ patients, suggesting that RPE-signaling may even be super-normal, in the case of loss-avoidance. The observation that instances of loss-avoidance evoke stronger frontostriatal responses in individuals with more severe negative symptoms suggests a mechanism by which motivational deficits may emerge from excessive avoidance-learning in SZ.